Efficacy of first-line ART regimens based on tenofovir in HIV-infected patients with pre-existing A62V mutation in reverse transcriptase.

INTRODUCTION: The amino acid substitution A62V in reverse transcriptase was identified as a mutation correlated with virologic failure in patients on first-line therapy including tenofovir (TDF) and tenofovir alafenamide (TAF). A62V is a typically polymorphic mutation in HIV-1 sub-subtype A6, which is the most widespread virus variant in Russia. MATERIALS AND METHODS: The European EuResist (EIDB) database was queried to form two equivalent groups of patients: group 1 ‒ patients with A62V at baseline treated with TDF or TAF on the first-line therapy, group 2 ‒ patients without A62V at baseline treated with TDF or TAF on the first-line therapy. Each group included 23 patients. RESULTS: There was no statistical difference between the two groups in virologic efficacy in 4, 12, and 24 weeks after the start of antiretroviral therapy (ART) and in the frequency of virologic failures. CONCLUSION: This study has some limitations, and the exact role of A62V in the efficacy of the first-line ART based on tenofovir deserves further investigation.

[Nutrition of pregnant. Comparative analysis based on data from a survey of residents of Russian Federation and the Republic of Azerbaijan (on the example of Astrakhan and Baku)].

Poor nutrition of the expectant mother leads to an unfavorable course of pregnancy and a number of serious deviations in the development of the child. Therefore, a multifaceted study of the actual nutrition of a pregnant woman is relevant, including the identification of trends associated with geographical, ethnic, and family characteristics. The study was aimed at conducting a comparative analysis of the nutrition of pregnant women from two cities, Astrakhan (Russian Federation) and Baku (Republic of Azerbaijan), by means of a questionnaire. Material and methods. In the course of a voluntary anonymous survey in 2022, 432 women aged 18-50 years old in the II trimester of pregnancy, living in Baku (n=280, group 1) and Astrakhan (n=152, group 2) have been interviewed. The answers of the respondents were analyzed in terms of eating habits, frequency of intake and food repertoire. Results. An analysis of the nutrition of pregnant women from both cities showed that it is unbalanced in terms of a set of products. Significant violations of the diet were noted in women from both studied groups, for example, a reduction in its multiplicity to two times a day (in group 1 - 2.5% and in group 2 - 7.2%). When conducting a comparative analysis of the nutrition of expectant mothers using the Pearson χ-square contingency coefficient, it was found that the groups had no significant differences in the consumption of milk and dairy products, meat and meat products, fish and seafood. Meat and meat products were used daily by no more than 31% of the surveyed, milk and dairy products - 43%, about half of pregnant women didn't consume fish and seafood. A relationship was established between the frequency of fruit consumption and the city of residence of pregnant women, in Baku women consumed fruits more often. In both groups, the abuse of confectionery and sugar was noted, some women already suffered from diabetes (5.4% from Astrakhan and 0.7% from Baku). Digestive pathology was detected in group 1 - in 11.2% (17), in group 2 - in 29.3% (79) of pregnant women. When conducting a comparative analysis of the frequency of consumption of undesirable products (mayonnaise, sauces, chips, carbonated drinks), it turned out that the groups were homogeneous, no connection with the city of residence was established. During pregnancy, 40.1 and 45.0% of women from 1 and 2 groups, respectively, took vitamin-mineral complexes. The level of vitamin D in the blood serum was determined by 29.6 and 6.8% of the respondents, respectively. A comparative analysis of the content of vitamin D in blood serum, determined respectively in 29.6 and 6.8% of respondents, showed that the groups of subjects were homogeneous, no connection of vitamin D level with the city of residence was found. Conclusion. In general, all the peculiarities of pregnant women's nutrition identified in the course of the survey can lead to an imbalance in the diet in terms of nutrient content, a deficiency of complete proteins, vitamins, and trace elements with excessive consumption of carbohydrates. When conducting a comparative analysis, it was possible to identify differences in the diet of pregnant women, relating only to the consumption of fruits - some respondents from Astrakhan consumed fruits less than once a week. Common unfavorable factors for pregnant women of both groups were the abuse of "undesirable" products, flour products and sugar, as well as the lack of involvement of women in the examination to assess the body's vitamin D supply and the rare prescription of vitamin-mineral complexes by specialists to correct micronutrient deficiencies.

[Genetic diversity of capsid protein (p24) in human immunodeficiency virus type-1 (HIV-1) variants circulating in the Russian Federation].

INTRODUCTION: The human immunodeficiency virus (HIV) protein p24 plays an important role in the life cycle of the virus, and also is a target for diagnostic tests and for new antiretroviral drugs and therapeutic vaccines. The most studied variant of HIV-1 in the world is subtype B. In Russia, the most common variant is A6, the spread of recombinant forms (CRF63_02A6, CRF03_A6B) is observed as well as circulation of G and CRF02_AG variants. However, a detailed study of the p24 protein in these variants has not yet been conducted. The aim was to study the features of the p24 protein in HIV-1 variants circulating in Russia and estimate the frequency of occurrence of pre-existing mutations associated with resistance to lenacapavir, the first antiretroviral drug in the class of capsid inhibitors. MATERIALS AND METHODS: The objects of the study were the nucleotide sequences obtained from the Los Alamos international database and clinical samples from HIV infected patients. RESULTS AND DISCUSSION: The features of HIV-1 variants circulating in Russia have been determined. V86A, H87Q, I91F are characteristic substitutions in A6 genome. It is shown that the presence of preexisting mutations associated with resistance to lenacapavir is unlikely. CONCLUSION: Features of the p24 protein in HIV-1 variants circulating in Russia allow them to be distinguished from others variants and among themselves. The prognosis for the use of lenacapavir in Russia is generally favorable. The results obtained could be taken into account in developing and using antiretroviral drugs and therapeutic vaccines.

[Agomelatine in the treatment of major depressive disorder: assessment of the efficacy and tolerability]. / Agomelatin pri lechenii bol'shogo depressivnogo rasstroistva: otsenka éffektivnosti i perenosimosti.

Agomelatine is an antidepressant agent with an innovative unique pharmacodynamic profile, including melatonergic receptor agonism (MT1 / MT2) and antagonistic effects on serotonergic 5-HT2C receptors. According to the results of meta-analyzes of clinical studies of the acute phase of a major depressive disorder, the antidepressant effect of agomelatine itself is significantly higher than that of placebo, but somewhat inferior to a number of other antidepressants (especially SSRIs and venlafaxine). To date, there is some uncertainty regarding the efficacy of agomelatine for the prevention of recurrence of MDD and its hepatotoxicity profile. In this regard, agomelatine is not considered as a drug of first choice in treatment of MDD. However, the heterogeneous clinical manifestations of MDD and the unique mechanism of action of agomelatine with the ability of the drug to have a modulating effect on sleep, make it possible to effective use it for treating such disorders. In addition, agomelatine has a more favorable safety profile, which allows considering it as a drug of choice in patients who have contraindications to other antidepressants or in the absence of therapeutic response to another antidepressant therapy.

[The differences in the estimation of depression severity by psychiatrists and patients during the combined treatment with agomelatine (a multicenter study "EMOTSIA")]. / Razlichiya v otsenke tyazhesti depressii vrachami i patsientami v protsesse kombinirovannoi terapii agomelatinom (mul'titsentrovoe issledovanie «EMOTsIYa¼).

AIM: To compare the prognosis of depression severity estimated by the physician and by the patient based on the treatment outcome. MATERIAL AND METHODS: One hundred and seven patients with depression were examined. Mental status was assessed with HАМ-D, SHAPS, CGI-S, CGI-I, PGI-S, PGI-I and VAS. A data analysis was performed. RESULTS: There were differences in the estimation of depression severity by psychiatrists and patients. Moreover, the scores on HАМ-D and CGI-S were not consistent when assessed by psychiatrists. As the severity of depression decreased and patient's state improved during the treatment with agomelatine (valdoxan), the assessments of the changes by the psychiatrist and the patient became similar. CONCLUSION: Agomelatine (valdoxan) is effective and tolerable in the treatment of depression of any severity. The differences between the psychiatrist's and patient's estimation of the depression severity at baseline using different psychometric scales can level the prognostic value of treatment outcome.

[A delayed motor production of open chains of linear strokes presented visually in static and dynamic modes: a comparison between 9 to 11 years old children and adults].

The production of drawing movements was studied in 29 right-handed children of 9-to-11 years old. The movements were the sequences of horizontal and vertical linear stokes conjoined at right angle (open polygonal chains) referred to throughout the paper as trajectories. The length of a trajectory varied from 4 to 6. The trajectories were presented visually to a subject in static (linedrawing) and dynamic (moving cursor that leaves no trace) modes. The subjects were asked to draw (copy) a trajectory in response to delayed go-signal (short click) as fast as possible without lifting the pen. The production latency time, the average movement duration along a trajectory segment, and overall number of errors committed by a subject during trajectory production were analyzed. A comparison of children's data with similar data in adults (16 subjects) shows the following. First, a substantial reduction in error rate is observed in the age range between 9 and 11 years old for both static and dynamic modes of trajectory presentation, with children of 11 still committing more error than adults. Second, the averaged movement duration shortens with age while the latency time tends to increase. Third, unlike the adults, the children of 9-11 do not show any difference in latency time between static and dynamic modes of visual presentation of trajectories. The difference in trajectory production between adult and children is attributed to the predominant involvement of on-line programming in children and pre-programming in adults.

[Peculiarities of saliva chemiluminescence and microelement hair content in children with various dental caries activity].

Integrated stomatological examination of 1002 children of Khabarovsk Territory was conducted. Besides carious process and oral hygiene indices the intensity of free radical oxidation in saliva (by chemiluminescence method) and basic microelement hair content (by spectral analysis method) in urban and rural children with compensated and decompensated forms of dental caries. High and equal prevalence and incidence of dental caries in urban and rural children was found. It was shown that in cases of decompensated forms of dental caries indicators of saliva chemiluminescence and consequently the intensity of free radical oxidation was significantly higher than in cases of compensated forms of dental caries. It was determined that activation of free radical oxidation with dental caries progression was developed on the background of combined deficit and imbalance of essential microelements.

Assessment of effectivity of oral killed typhoid and paratyphoid B vaccines and aerosol chemical typhoid vaccine in controlled field trials.

A total of 3 controlled field trials were carried out. One of them (1963) showed that aerosol chemical typhoid vaccine did not protect vaccinated subjects from the disease. Two other tests (1964 and 1965) assessing the effectivity of killed orally administered typhoid vaccine revealed a short term (up to 3 months) protective effect expressed by an effectivity coefficient of 45%, fiducial limits being 8-70%. In the assessment of oral paratyphoid B vaccine, the difference in morbidity in the experimental and control groups was statistically insignificant due to a small number of cases of disease.

Controlled field trials of killed oral typhoid and paratyphoid B vaccines and cell-free, chemical aerosol typhoid vaccine.

Three controlled field trials were carried out. One of them (1963) showed that an aerosol with cell-free, chemical typhoid vaccine did not protect vaccinees from the disease. The other trials (1964 and 1965) assessing the efficacy of killed oral typhoid vaccine revealed a short term (up to 3 months) protective effect. In the trial of oral paratyphoid B vaccine no statistically significant difference in morbidity in the test and control groups was observed due to the small number of cases.

Assessment of effectivity of oral killed typhoid and paratyphoid b vaccines and aerosol chemical thyphoid vaccine in controlled field trials.

A total of 3 controlled field trials were carried out. One of them (1963) showed that aerosol chemical typhoid vaccine did not protect vaccinated subjects from the disease. Two other tests (1964 and 1965) assessing the effectivity of killed orally administered typhoid vaccine revealed a short term (up to 3 months) protective effect expressed by an effectivity coefficient of 45%, fiducial limits being 8-70%. In the assessment of oral paratyphoid B vaccine, the difference in morbidity in the experimental and control groups was statistically insignificant due to a small number of cases of disease.

A controlled field trial and laboratory study of five typhoid vaccines in the USSR.

A controlled field trial of typhoid vaccines was carried out in the USSR in 1962. It was the fifth and last of a series. Five preparations were tested, the most effective being a heat-killed divalent vaccine prepared from aerated broth culture. The results of a laboratory study of the vaccines were not in complete agreement with the data from the field trial. No correlation was found between the effectiveness of vaccines and the data from laboratory tests as to their potency, and the authors suggest that differences in effectiveness may be due to varying degrees of damage to biological components during the different production processes. The effectiveness is also sensitive to dosage.